Clinical observations have strongly implicated a number of anticonvulsants as human teratogens. Compounds from 3 classes of anticonvulsants: oxazolidinediones, hydantoins, and succinimides together with phenacemide and valproic acid have been evaluated, and found to be embryotoxic in a dose related manner in the CD-1 mouse. Following i.p. administration, these compounds produced not only intrauterine growth retardation, but also a range of congenital abnormalities. Defects of the skeletal system were primarily the result of treatment during early organogenesis while treatment during late organogenesis produced predominately cleft palates. Estimation of the relative teratogenic potentials of these compounds showed teratogens in the mouse. Treatment of the dams on days 8-10 of pregnancy with valproic acid produced high incidences of exencephaly. Postimplantation mouse embryos,, cultured in the presences of valproic acid produced defects in the neural tube. These defects were similar to those observed following treatment in vivo. This suggest a direct dysmorphogenic action of valproic acid on the central nervous system producing the condition described as exencephaly.